Transcriptional regulation of Shigella virulence plasmid-encoded genes by VirB and CRP

摘要

Shigella flexneri is a species of Gram-negative intracellular pathogens that causes bacillary dysentery in humans. Shigella relies on the precise transcriptional regulation of virulence genes, encoded by a large virulence plasmid, for invasion and infection of human colonic epithelial cells. The transcription of most identified virulence genes are regulated through a cascade controlled by the primary regulator of virulence genes, VirF, and the global transcriptional regulator, VirB. Currently, few studies have addressed how individual Shigella virulence genes are precisely regulated for optimal expression during specific stages of pathogenesis and within the constraints of the regulatory cascade. This work addresses how individual virulence genes are regulated through the study of transcriptional regulation in four Shigella virulence genes, icsP, ipaJ, phoN1, and ipaH7.8. Analysis of the icsP gene has identified multiple promoters contributing to icsP transcription and to the regulation of IcsP protein production through the use of two different translation start sites. In addition, analyses of the ipaJ, phoN1, and ipaH7.8 genes has identified that the phoN1 gene is transcriptionally regulated by the CRP, suggesting that catabolite repression is involved with the regulation of some virulence genes in Shigella. Together, these data suggest that the transcriptional regulation of virulence genes in Shigella flexneri is more complex than previously observed.